What treatments improve outcomes in acute myocardial infarction?

BENEFICIAL

Angiotensin-Converting Enzyme (ACE) Inhibitors

One overview and one systematic review (in people treated within 36 hours to 14 days of acute myocardial infarction) have found that ACE inhibitors versus placebo significantly reduce mortality after 30 days. However, the overview also found that ACE inhibitors versus placebo significantly increase persistent hypotension and renal dysfunction. Whether ACE inhibitors should be offered to everyone presenting with acute myocardial infarction or only to people with signs of heart failure remains unresolved.

Aspirin

One systematic review in people with acute myocardial infarction has found that aspirin versus placebo significantly reduces mortality, nonfatal reinfarction, and nonfatal stroke at one month.

Beta Blockers

Two systematic reviews and one subsequent randomized controlled trial (RCT) have found that beta blockers versus control given within hours of acute myocardial infarction significantly reduce mortality and reinfarction. One RCT in people receiving thrombolytic treatment found that immediate versus delayed treatment with metoprolol significantly reduced rates of reinfarction and recurrent chest pain at six days, but had no significant effect on mortality at six days or at one year. One RCT comparing carvedilol with placebo in people with recent myocardial infarction and left ejection fraction of 40 percent or less receiving thrombolytic treatment found no significant difference in the combined end point of all cause mortality and hospital admission for any cardiovascular event after a median of 1.3 years, although mortality alone and recurrent non-fatal myocardial infarction were significantly lower with carvedilol.

Two systematic reviews have found that primary percutaneous transluminal coronary angioplasty versus primary thrombolysis significantly reduces mortality and reinfarction at 30 days in people with acute myocardial infarction. However, the trials were conducted mainly in specialist centers. The effectiveness of percutaneous transluminal coronary angioplasty versus thrombolysis in less specialized centers remains uncertain.

Thrombolysis

One overview of RCTs in people with acute myocardial infarction and ST elevation or bundle branch block on their initial electrocardiogram has found that prompt thrombolytic treatment (within six hours and perhaps up to 12 hours and longer after the onset of symptoms) versus placebo significantly reduces short-term mortality. The overview found that thrombolytic treatment versus control significantly increased the risk of stroke or major bleeding. Metaanalysis of RCTs comparing different types of thrombolytic agents versus each other have found no significant difference in mortality.

LIKELY TO BE BENEFICIAL

Nitrates in the Absence of Thrombolysis

One systematic review of the trials conducted in the prethrombolytic era found that nitrates versus placebo significantly reduce the risk of mortality in people with acute myocardial infarction.

UNLIKELY TO BE BENEFICIAL

Nitrates in Addition to Thrombolysis

Two RCTs from the thrombolytic era comparing nitrates with placebo in people with acute myocardial infarction found no significant difference in mortality.

TRADE OFF BETWEEN BENEFITS AND HARMS

Glycoprotein IIb/IIIa Inhibitors

Two large RCTs have found that combined treatment with half-dose thrombolysis plus abciximab does not reduce mortality at one month compared with full-dose thrombolysis in people with acute myocardial infarction, but may prevent non-fatal cardiovascular events. However, the RCTs found that combined treatment with abciximab increased bleeding complications, particularly extracranial hemorrhage. Three RCTs found conflicting evidence about the benefits of adding abciximab to primary coronary angioplasty or stenting in people with acute myocardial infarction, although all of the trials found that adding abciximab increased bleeding risk.

LIKELY TO BE INEFFECTIVE OR HARMFUL

Calcium Channel Blockers

Nine RCTs in people within the first few days of an acute myocardial infarction have found that neither dihydropyridines nor verapamil reduce mortality compared with placebo. In people with left ventricular dysfunction, one RCT found limited evidence that nifedipine given in the first few days after myocardial infarction may increase mortality compared with placebo.

BENEFICIAL

Early Invasive Cardiac Revascularization

One large RCT in people with cardiogenic shock within 48 hours of acute myocardial infarction has found that early invasive cardiac revascularization versus initial medical treatment alone significantly reduces mortality after six and 12 months. A second smaller RCT found similar results, although the difference was not significant.

UNKNOWN EFFECTIVENESS

Intra-aortic Balloon Counterpulsation

One abstract of an RCT comparing intra-aortic balloon counterpulsation plus thrombolysis versus thrombolysis alone in people with cardiogenic shock following acute myocardial infarction found no significant difference in mortality after six months.

Cardiac Transplantation; Early Cardiac Surgery; Positive Inotropes and Vasodilators; Pulmonary Artery Catheterization; Ventricular Assistance Devices. We found no evidence from RCTs about the effects of these interventions.

UNLIKELY TO BE BENEFICIAL

Thrombolysis

Subgroup analysis of people with cardiogenic shock after acute myocardial infarction from one RCT comparing thrombolysis versus no thrombolysis found no significant difference in mortality after 21 days.

Definition

Acute Myocardial Infarction

The sudden occlusion of a coronary artery leading to myocardial cell death.

Cardiogenic Shock

Defined clinically as a poor cardiac output plus evidence of tissue hypoxia that is not improved by correcting reduced intravascular volume.1 When a pulmonary artery catheter is used, cardiogenic shock may be defined as a cardiac index below 2.2 liters per minute per m2 despite an elevated pulmonary capillary wedge pressure (15 mm Hg).1–3

Incidence/Prevalence

Acute Myocardial Infarction

This is one of the most common causes of mortality worldwide. In 1990, ischemic heart disease was the world's leading cause of death, accounting for about 6.3 million deaths. The age standardized incidence varies among and within countries.4 Each year, about 900,000 people in the United States experience acute myocardial infarction of whom about 225,000 die. About one half of these people die within one hour of symptoms and before reaching a hospital emergency department.5 Event rates increase with age for both sexes and are higher in men than in women and in poorer than in richer people at all ages. The incidence of death from acute myocardial infarction has fallen in many Western countries during the past 20 years.

Cardiogenic Shock

Cardiogenic shock occurs in about 7 percent of people admitted to the hospital with acute myocardial infarction.6 Of these, about one half have established cardiogenic shock at the time of admission, and most of the others develop it during the first 24 to 48 hours of their admission.7

Etiology/Risk Factors

Acute Myocardial Infarction

The immediate mechanism of acute myocardial infarction is rupture of an atheromatous plaque causing thrombosis and occlusion of coronary arteries and myocardial cell death. Factors that may convert a stable plaque into an unstable plaque (the “active plaque”) have yet to be fully elucidated. Shear stresses, inflammation, and autoimmunity have been proposed. The changing rates of coronary heart disease in different populations are only partly explained by changes in the standard risk factors for ischemic heart disease (particularly fall in blood pressure and smoking).

Cardiogenic Shock

Cardiogenic shock after acute myocardial infarction usually follows a reduction in functional ventricular myocardium, and is caused by left ventricular infarction (79 percent of people with cardiogenic shock), more often than by right ventricular infarction (3 percent of people with cardiogenic shock).8 Cardiogenic shock after acute myocardial infarction also may be caused by cardiac structural defects, such as mitral valve regurgitation caused by papillary muscle dysfunction (7 percent of people with cardiogenic shock), ventricular septal rupture (4 percent of people with cardiogenic shock), or cardiac tamponade following free cardiac wall rupture (1 percent of people with cardiogenic shock). Major risk factors for cardiogenic shock after acute myocardial infarction are previous myocardial infarction, diabetes mellitus, advanced age, hypotension, tachycardia or bradycardia, congestive heart failure with Killip class II or III, and low left ventricular ejection fraction (ejection fraction <35 percent).7,8

Cardiogenic Shock

Mortality rates for people in the hospital with cardiogenic shock after acute myocardial infarction vary between 50 and 80 percent.2,3,6,7 Most deaths occur within 48 hours of the onset of shock.9 People surviving until discharge from the hospital have a reasonable long-term prognosis (88 percent survival at one year).10

5. National Heart, Lung, and Blood Institute. Morbidity and mortality: chartbook on cardiovascular, lung, and blood diseases. Bethesda, Md: U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health; May 1992.

10. Berger PB,
Tuttle RH,
Holmes DR,
et al.
One year survival among patients with acute myocardial infarction complicated by cardiogenic shock, and its relation to early revascularisation: results of the GUSTO-1 trial Circulation.
1999;99:873–8

This is one in a series of chapters excerpted from Clinical Evidence Concise, published by the BMJ Publishing Group, Tavistock Square, London, United Kingdom. Clinical Evidence Concise is published in print twice a year and is updated monthly online. Each topic is revised every eight months, and users should view the most up-to-date version at www.clinicalevidence.com. If you are interested in contributing to Clinical Evidence, please contact Claire Folkes (cfolkes@bmjgroup.com). This series is part of the AFP's CME. See “Clinical Quiz” on page 417.